Skip to main content
SpringerLink
Log in

Evaluation of behavior and endocrinological changes after REM sleep deprivation-induced mania-like behavior in mice

  • Original Article
  • Published:
Sleep and Biological Rhythms Aims and scope Submit manuscript

Abstract

The pressure to stay up longer in our modern society due to constant exposure to artificial light and interactive activities; furthermore, social and economic pressures impact human physiology and behavior. Rapid eye movement sleep deprivation (REMSD) alters most of the hormones, which may have adverse behavioral changes and other health consequences like mania and other psychiatric disorders. The exact role of REMSD-altered hormonal levels and the manner in which emerging consequences lead to mania-like behavior is poorly understood. Thus, we sought to verify the behavior and endocrinological changes after 48, 72, and 96 h of REMSD-induced mania-like behavior in mice. We performed modified multiple platform method of depriving the REM sleep for 48, 72 and 96 h, respectively, and one group maintained as a control. Motor assessment and aggressive behavior were determined by IR-Actimeter and Resident Intruder Test. Quantitative determination of serum thyroid hormones (TSH, T4, and T3), testosterone, corticosterone (CORT), prolactin (PRL), adrenocorticotropic hormone (ACTH), oxytocin (OT) and melatonin (MT) concentrations were determined by ELISA method. After respective hours of REMSD, the higher locomotion noticed among all REMSD mice and also showed higher aggressive behavior compared with control. Concentration of serum TSH and T4 was declined and elevated the T3, PRL, CORT, testosterone, ACTH, OT and MT levels in REMSD mice. These experiments showed that concentrations for the majority of the studied hormone and behavior were disrupted during REMSD. Our study indicated that REMSD results in mania-like behavior in mice and associated disruption to hormonal levels, although the exact mechanisms by which these take place remain to be determined.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. McNamara P, Capellini I, Harris E, Nunn CL, Barton RA, Preston B. The phylogeny of sleep database: a new resource for sleep scientists. Open Sleep. 2008;J1:11–4.

    Google Scholar 

  2. Hublin C, Kaprio J, Partinen M, Koskenvuo M. Insufficient sleep—a population-based study in adults. Sleep. 2001;24(4):392–400.

    Article  CAS  PubMed  Google Scholar 

  3. Rajaratnam SM, Arendt J. Health in a 24-h society. Lancet. 2001;358(9286):999–1005.

    Article  CAS  PubMed  Google Scholar 

  4. National Health Interview Survey. Quickstats: percentage of adults who reported an average of < 6 hours of sleep per 24-hour period bSaAG-US. Morb Mortal Wkly Rep. 2005; 54: 933.

    Google Scholar 

  5. Harvey AG. Sleep and circadian rhythms in bipolar disorder: seeking synchrony, harmony, and regulation. Am J Psychiatry. 2008;165(7):820–9.

    Article  PubMed  Google Scholar 

  6. Reiser R, Thompson LW. Bipolar disorder: advances in psychotherapy-evidence-based practice. Cambridge: Hogrefe& Huber Publishers; 2005.

    Google Scholar 

  7. Murray CJ, Lopez AD. The global burden of disease. Geneva: World Health Organization Eds.; 1996; pp. 21–2.

    Google Scholar 

  8. Osby U, Brandt L, Correia N, Ekbom A, Sparen P. Excess mortality in bipolar and Unipolar disorder in Sweden. Arch Gen Psychiatry. 2001;58(9):844–50.

    Article  CAS  Google Scholar 

  9. Muller-Oerlinghausen B, Berghofer A, Bauer M. Bipolar disorder. Lancet. 2002;359:241–7.

    Article  PubMed  Google Scholar 

  10. Kessler L, Nedeltcheva A, Imperial J, Penev PD. Changes in serum TSH and free T4 during human sleep restriction. Sleep. 2010;33:1115–8.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Everson CA, Nowak TS Jr. Hypothalamic thyrotropin-releasing hormone mRNA responses to hypothyroxinemia induced by sleep deprivation. Am J Physiol Endocrinol Metab. 2002;283:E85–E93.

    Article  CAS  PubMed  Google Scholar 

  12. Balzano S, Bergmann BM, Gilliland MA, Silva JE, Rechtschaffen A, Refetoff S. Effect of total sleep deprivation on 5-deiodinase activity of rat brown adipose tissue. Endocrinology. 1990;127:882–90.

    Article  CAS  PubMed  Google Scholar 

  13. Boral GC, Gosh AB, Pal SK, Gosh KK, Nandi DN. Thyroid function in different psychiatric disorders. Indian J Psychiatry. 1980;22:200–2.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Pope HG Jr, Kouri EM, Hudson JI. Effects of supraphysiologic doses of testosterone on mood and aggression in normal men: a randomized controlled trial. Arch Gen Psychiatry. 2000;57(2):133e40.

    Article  Google Scholar 

  15. Su TP, Pagliaro M, Schmidt PJ, Pickar D, Wolkowitz O, Rubinow DR. Neuropsychiatric effects of anabolic steroids in male normal volunteers. J Am Med Assoc. 1993;269(21):2760e4.

    Article  Google Scholar 

  16. Yates WR, Perry PJ, MacIndoe J, Holman T, Ellingrod V. Psychosexual effects of three doses of testosterone cycling in normal men. Biol Psychiat. 1999;45(3):254e60.

    Article  Google Scholar 

  17. Weiss EL, Bowers MB Jr, Mazure CM. Testosterone-patch-induced psychotic mania. Am J Psychiatry. 1999;156(6):969.

    Article  CAS  PubMed  Google Scholar 

  18. Schmidt M, Sofronescu A, Short B, Nahas Z, Zhu Y. Increased prolactin concentrations in a patient with bipolar disorder. Clin Chem. 2013;59(3):473–7.

    Article  CAS  PubMed  Google Scholar 

  19. Andersen ML, Martins PJ, D’Almeida V, Bignotto M, Tufik S. Endocrinological and catecholaminergic alterations during sleep deprivation and recovery in male rats. J Sleep Res. 2005;14(1):83–90.

    Article  PubMed  Google Scholar 

  20. Mikics E, Kruk MR, Haller J. Genomic and non-genomic effects of glucocorticoids on aggressive behavior in male rats. Psychoneuroendocrinology. 2004;29(5):618–35.

    Article  CAS  PubMed  Google Scholar 

  21. Linkowski P, Geenen V, Kerkhofs M, Mendlewicz J, Legros JJ. Cerebrospinal fluid neurophysins in affective illness and in schizophrenia. Eur Arch Psychiatry NeurolSci. 1984;234(3):162–5.

    Article  CAS  Google Scholar 

  22. Kim Y, McGee S, Czeczor JK, Czeczor JK, Walker AJ, Kale RP, Kouzani AZ, Walder K, Berk M, Tye SJ. Nucleus accumbens deep-brain stimulation efficacy in ACTH-pretreated rats: alterations in mitochondrial function relate to antidepressant-like effects. Transl Psychiatry. 2016;6:e842.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Jouvet D, Vimont P, Delorme F, Jouvet M. Study of selective deprivation of the paradoxal sleep phase in the cat. C R Seances Soc Biol Fil. 1964;158:756–9.

    CAS  PubMed  Google Scholar 

  24. Zager A, Andersen ML, Ruiz FS, Antunes IB, Tufik S. Effects of acute and chronic sleep loss on immune modulation of rats. Am J Physiol Regul Integr Comp Physiol. 2007;293(1):R504-9.

    Article  CAS  PubMed  Google Scholar 

  25. Nasir MN, Abdullah J, Habsah M, Ghani RI, Rammes G. Inhibitory effect of asiatic acid on acetylcholinesterase, excitatory post synaptic potential and locomotor activity. Phytomedicine. 2012;19(3–4):311–6.

    Article  CAS  PubMed  Google Scholar 

  26. Meyer N, Jenikejew J, Richter SH, Kaiser S, Sachser N. Social experiences during adolescence affect anxiety-like behavior but not aggressiveness in male mice. Behav Brain Res. 2017;326(9):147–53.

    Article  PubMed  Google Scholar 

  27. Ghosh PK, Biswas NM, Ghosh D. Effect of lithium chloride on testicular steroidogenesis and gametogenesis in immature male rats. ActaEndocrinol (Copenh). 1991;124:76–82.

    CAS  Google Scholar 

  28. Belete H, Mulat H, Fanta T, Yimer S, Shimelash T, Ali T, Tewabe T. Magnitude and associated factors of aggressive behaviour among patients with bipolar disorder at A manual Mental Specialized Hospital, outpatient department, Addis Ababa, Ethiopia: cross-sectional study BMC. Psychiatry. 2016;16(1):443.

    PubMed  Google Scholar 

  29. Rodrigues NC, da Cruz NS, de Paula Nascimento C, da Conceição RR, da Silva AC, Olivares EL, Marassi MP. Sleep deprivation alters thyroid hormone economy in rats. Exp Physiol. 2015;100(2):193–202.

    Article  CAS  PubMed  Google Scholar 

  30. Boral GC, Gosh AB, Pal SK, Gosh KK, Nandi DN. Thyroid function in different psychiatric disorders. Indian J Psychiatry. 1980;22(2):200–2.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Evans DL, Strawn SK, Haggerty JJR, Garbutt JC, Burnett GB, Pedersen CA. Appearance of mania in drug-resistant bipolar depressed patients after treatment with l-triiodothyronine. J Clin Psychiatry. 1986;47(10):521–2.

    CAS  PubMed  Google Scholar 

  32. Ebinger M, Sievers C, Ivan D, Schneider HJ, Stalla GK. Is there a neuroendocrinological rationale for testosterone as a therapeutic option in depression? J Psychopharmacol. 2009;23(7):841–53.

    Article  CAS  PubMed  Google Scholar 

  33. Franzen PL, Buysse DJ, Dahl RE, Thompson W, Siegle GJ. Sleep deprivation alters pupillary reactivity to emotional stimuli in healthy young adults. Biol Psychol. 2009;80(3):300–5.

    Article  PubMed  Google Scholar 

  34. Kahn-Greene ET, Lipizzim EL, Conrad AK, Kamimori GH, Killgore WDS. Sleep deprivation adversely affects interpersonal responses to frustration. Personality Individ Differ. 2006;41:1433–43.

    Article  Google Scholar 

  35. Sher L, Grunebaum MF, Sullivan GM, Burke AK, Cooper TB, Mann JJ, Oquendo MA. Testosterone levels in suicide attempters with bipolar disorder. J Psychiatr Res. 2012;46(10):1267–71.

    Article  PubMed  Google Scholar 

  36. Mattsson A, Schalling D, Olweus D, Löw H, Svensson J. Plasma testosterone, aggressive behavior, and personality dimensions in young male delinquents. J Am Acad Child Psychiatry. 1980;19(3):476 – 90.

    Article  CAS  PubMed  Google Scholar 

  37. Fratta W, Collu M, Martellotta MC, Pichiri M, Muntoni F, Gessa GL. Stress-induced insomnia: opioid–dopamine interactions. Eur J Pharmacol. 1987;3:437–40.

    Article  Google Scholar 

  38. Gessa GL, Pani L, Fadda P, Fratta W. Sleep deprivation in the rat: an animal model of mania. Eur Neuropsychopharmacol. 1995;5:89–93.

    Article  CAS  PubMed  Google Scholar 

  39. Underwood RH, Williams GH. The simultaneous measurement of aldosterone, cortisol, and corticosterone in human peripheral plasma by displacement analysis. J Lab Clin Med. 1972;79:848–62.

    CAS  PubMed  Google Scholar 

  40. Whalley LJ, Christie JE, Blackwood DH, Bennie J, Dick H, Blackburn IM, Fink G. Disturbed endocrine function in the psychoses I: disordered homeostasis or disease process? Br J Psychiatry. 1989;155:455–61.

    Article  CAS  PubMed  Google Scholar 

  41. Torre DL, Falorni A. Pharmacological causes of hyperprolactinemia. Ther Clin Risk Manag. 2007;3(5):929–51.

    PubMed  PubMed Central  Google Scholar 

  42. Riecher-Rossler A, Rybakowski JK, Pflueger MO, Beyrau R, Kahn RS, Malik P, Fleischhacker WW. Hyperprolactinemia in antipsychotic naive patients with first-episode psychosis. Psychol Med. 2013;43(12):2571–82.

    Article  CAS  PubMed  Google Scholar 

  43. Schmidt M, Sofronescu A, Short B, Nahas Z, Zhu Y. Increased prolactin concentrations in a patient with bipolar disorder. Clin Chem. 2013;59(3):473–5.

    Article  CAS  PubMed  Google Scholar 

  44. Morton IK, Hall JM. Concise dictionary of pharmacological agents: properties and synonyms. New York: Springer Science & Business Media. 2012; p. 84.

    Google Scholar 

  45. Valvassori SS, Resende WR, Dal-Pont G, Sangaletti-Pereira H, Gava FF, Peterle BR, Carvalho AF, Varela RB, Dal-Pizzol F. Quevedo J. Lithium ameliorates sleep deprivation induced mania-like behavior, hypothalamic-pituitary-adrenal (HPA) axis alterations, oxidative stress and elevations of cytokine concentrations in the brain and serum of mice. Bipolar Disord. 2017;19(4):246–58.

    Article  CAS  Google Scholar 

  46. BelvederiMurri M, Prestia D, Mondelli V, Pariante C, Patti S, Olivieri B, Arzani C, Masotti M, Respino M, Antonioli M, Vassallo L, Serafini G, Perna G, Pompili M, Amore M. The HPA axis in bipolar disorder: systematic review and meta-analysis. Psychoneuroendocrinology. 2016;63:327 – 42.

    Article  CAS  Google Scholar 

  47. Geng W, Wu G, Huang F, Zhu Y, Nie J, He Y, Chen L. Sleep deprivation induces abnormal bone metabolism in temporomandibular joint. Int J ClinExp Med. 2015;8(1):395–403.

    CAS  Google Scholar 

  48. Carter CS. Oxytocin pathways and the evolution of human behavior. Annu Rev Psychol. 2014;65:17–39.

    Article  PubMed  Google Scholar 

  49. Turan T, Uysal C, Asdemir A, Kılıç E. May oxytocin be a trait marker for bipolar disorder? Psychoneuroendocrinology. 2013;38:2890–6.

    Article  CAS  PubMed  Google Scholar 

  50. Nurnberger JI Jr, Adkins S, Lahiri DK, Mayeda A, Hu K, Lewy A, Miller A, Bowman ES, Miller MJ, Rau L, Smiley C, Davis-Singh D. Melatonin suppression by light in euthymic bipolar and unipolar patients. Arch Gen Psychiatry. 2000;57(6):572–9.

    Article  CAS  PubMed  Google Scholar 

  51. Kennedy SH, Tighe S, McVey G, Brown GM. Melatonin and Cortisol “switches” during mania, depression and euthymia in a drug free bipolar patient. J Nerv Ment Dis. 1989;177:300–3.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

Department of Science and Technology (DST), INSPIRE division, New Delhi provided financial support as a fellowship (Grant Reference number—DST/INSPIRE/2014/IF140562). The funding source had no involvement in the preparation of the article, study design, analysis, interpretation of data and decision to submit the article for publication.

Author information

Authors and Affiliations

  1. Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamilnadu, 608 002, India

    Saiful Alom Siddique, Thangavel Tamilselvan, Manikkannan Vishnupriya & Elumalai Balamurugan

Authors
  1. Saiful Alom Siddique
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thangavel Tamilselvan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Manikkannan Vishnupriya
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elumalai Balamurugan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elumalai Balamurugan.

Ethics declarations

Conflict of interest

The authors declare that there are no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Siddique, S.A., Tamilselvan, T., Vishnupriya, M. et al. Evaluation of behavior and endocrinological changes after REM sleep deprivation-induced mania-like behavior in mice. Sleep Biol. Rhythms 16, 375–385 (2018). https://doi.org/10.1007/s41105-018-0166-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s41105-018-0166-6

Keywords

Search

Navigation